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Major progress has been made in the field of liver transplantation since the first procedure was performed nearly 50 years ago. Despite these improvements, renal dysfunction before and after liver transplantation remains a major complicating factor associated with increased health care costs, morbidity, and mortality. Creatinine-based estimates of renal function are inaccurate in the setting of end-stage liver disease and often lead to underdiagnosis and late intervention. This issue is critical in that it is important to understand both the etiology and chronicity of renal dysfunction before liver transplantation because the treatment clearly varies, especially with respect to simultaneous liver-kidney (SLK) transplantation. Because of the scarcity of available grafts, identifying appropriate candidates for SLK transplantation is crucial. Hepatorenal syndrome is common in liver transplant candidates; however, other etiologies of renal dysfunction need to be considered. Renal dysfunction after liver transplantation is common and may have an acute or chronic presentation. Although calcineurin inhibitors (CNIs) have been associated with post–liver transplant nephrotoxicity, their role may be overestimated, and other contributing etiologies should remain in a clinician's differential diagnosis. Alternatives to CNIs have been evaluated; however, a safe immunosuppressive regimen that achieves the preservation of renal function in liver transplant recipients remains to be established. In this review of the literature, renal dysfunction in the setting of liver transplantation is evaluated, and the critical issues that are barriers to improved outcomes are highlighted. Liver Transpl, 2012. © 2012 AASLD.